Connective tissue growth factor: Structure-function relationships of a mosaic, multifunctional protein

Connective tissue growth factor (CTGF) is a member of the CCN family of six small secreted, cysteine-rich growth factors. The unique modular structure encompasses distinct functional domains which enable CTGF to interact with growth factors, surface receptors and matrix components. Widely expressed, CTGF has critical roles in embryonic development and the maintenance of normal cell and connective tissue function. It is also important for tissue repair following injury, and has been implicated in common diseases including atherosclerosis, pulmonary and renal fibrotic disorders and cancer. Factors that regulate CTGF transcription in response to exogenous stimuli, as well as downstream signalling pathways, have been described. However, only recently have studies begun to unravel how the functional domains within the CTGF modules orchestrate signals and control key biological processes. This article highlights how the structural and functional domains of CTGF and CTGF cleavage fragments integrate multiple extracellular events into cell signals.